Respiratory therapies for amyotrophic lateral sclerosis: A primer

Respiratory complications are a common cause of morbidity and mortality in amyotrophic lateral sclerosis (ALS). Treatment of respiratory insufficiency with noninvasive ventilation (NIV) improves ALS patients' quality of life and survival. Evidence‐based practice guidelines for the management of ALS patients recommend treatment of respiratory insufficiency with NIV as well as consideration of insufflation/exsufflation to improve clearance of airway secretions. Despite these recommendations respiratory therapies remain underused. In this review we provide a practical guide for the clinician to prescribe and manage respiratory therapies for the patient with ALS. Muscle Nerve 46: 313–331, 2012Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93524/1/23282_ftp.pd

Novel mutations in the anoctamin 5 gene ( ANO5 ) associated with limb‐girdle muscular dystrophy 2L

Introduction: We present a Jordanian man with the typical LGMD 2L phenotype of early, asymmetric quadriceps weakness and subsequent biceps brachii weakness. Methods: Case report. Results: Muscle biopsies document a progressive dystrophic pattern unrelated to known sarcolemmal defects associated with muscular dystrophy. Genetic testing revealed novel, heterozygote Anoctamin 5 gene mutations. Conclusions: This case report expands the known mutations resulting in LGMD 2L and supports the assertion that Anoctamin 5 mutations are more prevalent than previously recognized. Muscle Nerve, 2013Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96310/1/23542_ftp.pd

Predictors of noninvasive ventilation tolerance in patients with amyotrophic lateral sclerosis

Noninvasive ventilation (NIV) appears to improve survival and quality of life in patients with amyotrophic lateral sclerosis (ALS), but little is known about predictors of NIV tolerance. NIV use was assessed and clinical predictors of tolerance were investigated, using predictive modeling, in ALS patients diagnosed and followed in our clinic until death over a 4-year time period. Patients were prescribed NIV based on current practice parameters when respiratory symptoms were present or forced vital capacity was less than 50%. We prescribed NIV in 52% (72) of patients. For those prescribed NIV, information regarding tolerance was available for 50 patients, with 72% (36) tolerant to its use. Tolerance was six times more likely in limb-onset than bulbar-onset ALS patients, with a trend toward reduced tolerance in those with lower forced vital capacity at NIV initiation. Age, gender, and duration of disease were not predictors of NIV tolerance. We conclude that a majority of ALS patients who are prescribed NIV can successfully become tolerant to its use. Muscle Nerve, 2005Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48760/1/20415_ftp.pd

The cost-effectiveness of early noninvasive ventilation for ALS patients

BACKGROUND: Optimal timing of noninvasive positive pressure ventilation (NIPPV) initiation in patients with amyotrophic lateral sclerosis (ALS) is unknown, but NIPPV appears to benefit ALS patients who are symptomatic from pulmonary insufficiency. This has prompted research proposals of earlier NIPPV initiation in the ALS disease course in an attempt to further improve ALS patient quality of life and perhaps survival. We therefore used a cost-utility analysis to determine a priori what magnitude of health-related quality of life (HRQL) improvement early NIPPV initiation would need to achieve to be cost-effective in a future clinical trial. METHODS: Using a Markov decision analytic model we calculated the benefit in health-state utility that NIPPV initiated at ALS diagnosis must achieve to be cost-effective. The primary outcome was the percent utility gained through NIPPV in relation to two common willingness-to-pay thresholds: $50,000 and$100,000 per quality-adjusted life year (QALY). RESULTS: Our results indicate that if NIPPV begun at the time of diagnosis improves ALS patient HRQL as little as 13.5%, it would be a cost-effective treatment. Tolerance of NIPPV (assuming a 20% improvement in HRQL) would only need to exceed 18% in our model for treatment to remain cost-effective using a conservative willingness-to-pay threshold of $50,000 per QALY. CONCLUSION: If early use of NIPPV in ALS patients is shown to improve HRQL in future studies, it is likely to be a cost-effective treatment. Clinical trials of NIPPV begun at the time of ALS diagnosis are therefore warranted from a cost-effectiveness standpoint